This is a revised lead application for the Advanced Glaucoma Intervention Study (AGIS) requesting support for participation by Georgetown University. It includes the revised AGIS Operations Manual and research plan and is supplemented by applications from a Coordinating Center and 9 other Clinical Centers. The qualifications of this institution to participate in AGIS are detailed, including patient availability. During the 18-month period ending June, 1986 96 AGIS-eligible eyes were treated by us, a rate of 64 eligible eyes per year; when AGIS begins we expect to be able to enroll at least 30 eyes per year of recruitment. The primary goal of the AGIS is to assess systematically the long- range outcomes of sequences of interventions in 840 eyes that have failed initial medical treatment for glaucoma. Eligible eyes will be randomly assigned to one of two intervention sequences: 1) trabeculectomy (T), followed by argon laser trabeculoplasty (ALT) should T fail, and followed by a second T should ALT fail; and 2) ALT followed by T should ALT fail, and followed by another T should the first T fail. Eyes that fail the assigned sequence of three interventions will be managed by additional surgery. The interventions will be supplemented with medical treatment as needed. During 5 years of followup we plan to determine degree of visual function loss, rates of failure of complications, and need for supplemental therapy. The prognostic value of ocular, systemic, personal and social factors, including compliance, will be studied. Participating institutions will adhere to common, specified definitions, eligibility criteria, methods of measurement, as well as diagnostic, treatment, quality control, and administrative procedures. A Coordinating Center will collect, process, and analyze study data and coordinate study activities; a Policy and Treatment Effects Monitoring Board will supervise the conduct of the study.